• Login as Editor
    View Item 
    •   Yeshiva Academic Institutional Repository
    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
    • View Item
    •   Yeshiva Academic Institutional Repository
    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    The regulation of human choline acetyltransferase

    Thumbnail
    Date
    1988
    Author
    Casper, Diana
    Metadata
    Show full item record
    Abstract
    Alzheimer's disease, a condition marked by progressive dementia, is due in part to a deficit in cholinergic metabolism in the basal forebrain. The most reliable marker for cholinergic neurons is choline acetyltransferase, abbreviated ChAT, the biosynthetic enzyme for acetylcholine synthesis. Levels of this enzyme are found to be reduced as much as 40 to 90 percent in the cortex of patients who die of Alzheimer's disease. It is with this interest that the following studies on the regulation of choline acetyltransferase are presented.;The regulation of choline acetyltransferase activity was studied in a human cholinergic neuroblastoma cell line, MC-IXC. It was found that cell passage, cell density, retinoic acid and sodium butyrate were able to increase ChAT activity on a per cell or per milligram protein basis. These activating conditions could only act on cell lines which already expressed some ChAT activity. In the cell culture system, retinoic acid and sodium butyrate activated ChAT to varying extents and had differential effects on acetylcholinesterase activity. The effects of retinoic acid and cell density were reversible by trypsinization of the cultures. Whereas other retinoids were able to stimulate ChAT activity, analogs of butyrate, such as gamma-amino butyric acid or beta-hydroxy butyrate were unable to mimic its effects. Serum deprivation and dimethylsulfoxide treatment were unable to stimulate ChAT activity.;Relying on specific activity as a probe for ChAT, the mechanism(s) by which retinoic acid and sodium butyrate was (were) able to stimulate ChAT activity was (were) further examined. Agents which inhibited mRNA or protein synthesis had no effect on the activation process. Retinoic acid and sodium butyrate treatment caused increases in the V{dollar}\sb{lcub}\rm max{rcub}{dollar} of ChAT but had no effect on the K{dollar}\sb{lcub}\rm m{rcub}{dollar} for either of its substrates. Agents which affect the activity of the protein kinase C or cyclic AMP-dependent protein kinase second messenger systems had no effect on the activation process, although retinoic acid treatment did result in a three-fold increase in cAMP levels. The evidence presented here suggests that ChAT activation by retinoic acid and sodium butyrate is post-translational in this neuroblastoma cell line.
    Permanent Link(s)
    https://yulib002.mc.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:8811010
    https://hdl.handle.net/20.500.12202/3189
    Collections
    • Albert Einstein College of Medicine: Doctoral Dissertations [1674]

    Yeshiva University Libraries copyright © 2021  DuraSpace
    YAIR Self-Deposit | YAIR User's Guide | Take Down Policy | Contact Us
    Yeshiva University
     

     

    Browse

    AllCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login as Editor

    Statistics

    View Usage Statistics

    Yeshiva University Libraries copyright © 2021  DuraSpace
    YAIR Self-Deposit | YAIR User's Guide | Take Down Policy | Contact Us
    Yeshiva University